Disease Information(sort of like the Intro to your MiniResearch Writeup):
Vibrio cholerae causes acute diarrhea by infecting human intestines and causes severe dehydration. The bacteria can thrive in human bodies and polluted water [1]. Even though the disease is rare in the United States, there is an increase in the number of cases around the world. Currently there are about 5 million cases and over 100,000 mortalities each year globally. Infection does not necessarily cause symptoms to appear. However, about 10% of the infected people will experience rapid loss of body fluids, electrolytes, and nutrients. Death can happen within several hours if treatment is not given. The disease is mostly diagnosed by stool sample. Cholera is a reportable disease in the United States and all samples are sent to state labs for subtyping. Current treatments include rehydration therapy, antibiotic treatment, and zinc treatment. However, antibiotic resistance has appeared in V. cholerae due to wide spread use of antibiotics [2]. https://www.ncbi.nlm.nih.gov/pubmed/28348025 [1] https://www.cdc.gov/cholera/index.html[2]
Previous studies:There are 162 studies on quinone reductase Essentiality of this protein:
NADH: ubiquinone oxidoreductase (Na ion pumping) serves as the main ion pump for the electrons entering the respiratory chain of a wide variety of disease causing bacteria. The protein works by creating a sodium gradient across membrane to maintain homeostasis, nutrition cotransport, ATP synthesis, flagella movements, and other vital functions[3]. The protein has also been found in Chlamydiophyla pneumoniae to help increase adaptive potential by maintaining internal homeostasis in environments with changing salinity and pH. This target can be inhibited to severely disrupt bacteria internal balance, thus impacting its ability to infect and adapt in the human body[4].
NCBI #:NC_005139.1
Protein ID (NP or XP #) or Wolbachia#:331633 (from NCBI)
Organism (including strain):Vibrio cholerae
Etiologic Risk Group (see link below):Group 2
http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/vibrio-cholerae-eng.php
Disease Information(sort of like the Intro to your MiniResearch Writeup):
Vibrio cholerae causes acute diarrhea by infecting human intestines and causes severe dehydration. The bacteria can thrive in human bodies and polluted water [1]. Even though the disease is rare in the United States, there is an increase in the number of cases around the world. Currently there are about 5 million cases and over 100,000 mortalities each year globally. Infection does not necessarily cause symptoms to appear. However, about 10% of the infected people will experience rapid loss of body fluids, electrolytes, and nutrients. Death can happen within several hours if treatment is not given. The disease is mostly diagnosed by stool sample. Cholera is a reportable disease in the United States and all samples are sent to state labs for subtyping. Current treatments include rehydration therapy, antibiotic treatment, and zinc treatment. However, antibiotic resistance has appeared in V. cholerae due to wide spread use of antibiotics [2].
https://www.ncbi.nlm.nih.gov/pubmed/28348025 [1]
https://www.cdc.gov/cholera/index.html[2]
Link to TDR Targets page (if present):n/a
Link to Gene Database page NCBI:https://www.ncbi.nlm.nih.gov/protein/BAB57768.1
Previous studies: There are 162 studies on quinone reductase
Essentiality of this protein:
NADH: ubiquinone oxidoreductase (Na ion pumping) serves as the main ion pump for the electrons entering the respiratory chain of a wide variety of disease causing bacteria. The protein works by creating a sodium gradient across membrane to maintain homeostasis, nutrition cotransport, ATP synthesis, flagella movements, and other vital functions[3]. The protein has also been found in Chlamydiophyla pneumoniae to help increase adaptive potential by maintaining internal homeostasis in environments with changing salinity and pH. This target can be inhibited to severely disrupt bacteria internal balance, thus impacting its ability to infect and adapt in the human body[4].
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096696[3]
https://www.ncbi.nlm.nih.gov/pubmed/?term=NADH%3Aubiquinone+reductase+(Na%2B-transporting)[4]
Is it a monomer or multimer as biological unit: Monomer in vibrio cholerae.
Complex of proteins?:Several subunits.
Druggable Target (list number or cite evidence from a paper/database showing druggable in another organism): https://www.ncbi.nlm.nih.gov/pubmed/28425301
*EC#:1.6.5.8
Link to BRENDA EC# page: http://www.brenda-enzymes.org/enzyme.php?ecno=1.6.5.8
Enzyme Assayinformation: Not specifically for 1.6.5.8, but there are many assay protocol for many different reductases on Sigma. There are assay protocols for the enzyme Vibrio cholerae.
-- links to assay reagents (substrates) pages.
http://www.brenda-enzymes.org/literature.php?e=1.6.5.8&r=725448
http://www.brenda-enzymes.org/literature.php?e=1.6.5.8&r=725538
--- List cost and quantity of substrate reagents, supplier, and catalog #
n/a
Structure (PDB or Homology model)
Similarity to Human: highest similarity 36.7% with OR51B6
Current Inhibitors:There are currently several inhibitors that are weak and have low binding affinity
Expression Information (has it been expressed in bacterial cells):yes
Purification Method: D-salt polyacrylamide 6000 gel filtration
http://www.brenda-enzymes.org/literature.php?e=1.6.5.8&r=674705
Image of protein (PyMol with features delineated and shown separately):
Figure 1. 3D image of NADH: ubiquinone reductase (Na+ transporting) of Vibrio cholerae from PDB, shown in cartoon in PyMol and colored by chain.
Amino Acid Sequence:
>tr|A0A177NCL7|A0A177NCL7_9GAMM Na(+)-translocating NADH-quinone reductase subunit E OS=Methylomonas koyamae GN=nqrE PE=3 SV=1MEAYIALFVKAVFIENLALSFFLGMCTFLAVSKKIATAMGLGVAVMVVQTLTVPANNFIY
QTLLKEDALSWLGITGVDLSFLSLLSCIGMIAAIVQILEMFLDKFVPALYNALGIFLPLI
TVNCAILAGSLFMIERDYNFGESVVYGIGSGFGWALAITLMAGVREKLKYSDVPAALQGL
GITFITAGLMSLGFMAFSGIQL
http://www.uniprot.org/uniprot/A0A177NCL7
Length of your protein in Amino Acids: 202
Molecular Weight of your protein in kiloDaltons: 27600 kDaltons
Molar Extinction coefficient of your protein at 280 nm wavelength: 20065 (http://web.expasy.org/cgi-bin/protparam/protparam)
TMpred graph Image (http://www.ch.embnet.org/software/TMPRED_form.html).
Figure 2. TMpred graph of Na(+) translocating NADH-quinone reductase subunit E from Methylomonas koyamae.
*CDS Gene Sequence (paste as text only):
>NC_005139.1:c2614943-2613720 Vibrio vulnificus YJ016 DNA, chromosome I, complete sequence
*GC% Content for gene: 46.16%
*GC% Content for gene (codon optimized): n/a